histidinohydroxylysinonorleucine and delta-hydroxylysylnorleucine

To determine the effects of percutaneous estradiol (E2) implants on the collagen composition and maturity in the bone and skin of osteoporotic postmenopausal women.. Sixteen postmenopausal women with low bone mineral density were treated for 1 year with 75-mg E2 implants. Iliac crest bone and skin biopsies were analyzed for collagen content and collagen cross-links before treatment and at 1 year. Dual energy x-ray absorptiometry of the lumbar spine and proximal femur was also performed before and after 1 year of therapy.. The cortical bone showed a significant increase in the mature cross-links of both hydroxylysylpyridinoline (P < .01) and lysylpyridinoline (P < .01), with a significant reduction in the percentage of collagen (P < .001). The pattern was similar in trabecular bone, with lysylpyridinoline increasing significantly (P < .05). The skin exhibited a significant reduction in the immature cross-link hydroxylysinonorleucine (P < .01), but no significant change in the percentage of collagen content or the mature cross-link histidinohydroxylysinonorleucine. The median increases in bone density were 11.5% at the spine and 4.34% at the total hip. The median post-treatment serum E2 level was 639 pmol/L.. Bone mineral density increased at all the sites measured in the spine and proximal hip. The quality of the collagen within the transiliac biopsies had matured in that the concentration of the mature collagen cross-links had increased. These findings support a reduction in the turnover of bone collagen following estrogen replacement therapy. More important, the formation of a more mature collagen fiber should help to reduce the risk of future bone fracture.

Topics: Absorptiometry, Photon; Administration, Cutaneous; Aged; Amino Acids; Bone and Bones; Bone Density; Collagen; Dipeptides; Estradiol; Estrogen Replacement Therapy; Female; Histidine; Humans; Osteoporosis, Postmenopausal; Skin; Time Factors

Keloid is a tissue with an excessive accumulation of collagen. In this study, we have partially characterized post-translational modifications of type I collagen in human keloid in order to pursue their potential involvement in this pathology. The levels of lysyl hydroxylation of the helical portions of alpha 1 and alpha 2 chains of type I collagen in keloid were significantly higher than those of normal, while the levels of prolyl hydroxylation were identical between these two groups. The contents of the major reducible cross-links in dermal collagen, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymero-desmosine, were both significantly higher in keloids (up to sixfold) than those of normal. In addition, significant amounts of hydroxylysine-aldehyde derived cross-links that are characteristic of skeletal tissue collagens, dehydro-dihydroxylysinonorleucine (about 0.3 mole/mole of collagen) and pyridinoline (about 0.1 mole/mole of collagen), were found in keloids. These results indicate that keloid-forming cells are phenotypically different from those in normal dermis and that the collagen produced is highly cross-linked. The increased cross-linking provides the fibrils with more stability that may result in an accumulation of collagen.

Topics: Adult; Amino Acids; Collagen; Cross-Linking Reagents; Desmosine; Dipeptides; Histidine; Humans; Hydroxylation; Hydroxylysine; Hydroxyproline; Keloid; Middle Aged; Protein Processing, Post-Translational; Protein Structure, Secondary; Skin

A high-performance liquid chromatographic-fluorescence detection method of reducible (immature) and nonreducible (mature and senescent) cross-links of collagen was established without the use of a radioisotope and preliminary fractionation step. This method used a gradient elution procedure of sodium citrate buffer containing 7% ethanol. The reducible cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, and lysinonorleucine) and nonreducible cross-link (histidinohydroxylysinonorleucine) were detected by O-phthalaldehyde derivatization with the postcolumn method, whereas other nonreducible cross-links (pyridinoline, deoxypyridinoline, and pentosidine) were detected by natural fluorescence. The linear ranges of contents of the O-phthalaldehyde derivative cross-links and the natural fluorescent nonreducible cross-links were 20-600, 5-500 (pyridinoline, deoxypyridinoline), and 0.2-20 pmol (pentosidine), respectively. Tissue containing 1-2 mg dry wt of collagen was adequate for duplicate analyses of the reducible and nonreducible cross-links. An equivalent of 0.25 mg of hydrolyzed collagen could be analyzed by this HPLC system. Using this system, age-related changes in the cross-links of collagen from human connective tissues were also investigated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Amino Acids; Arginine; Cartilage, Articular; Child; Child, Preschool; Chromatography, High Pressure Liquid; Collagen; Cross-Linking Reagents; Diaphyses; Dipeptides; Femur; Histidine; Humans; Indicators and Reagents; Infant; Lysine; Male; Middle Aged; Sensitivity and Specificity; Skin; Spectrometry, Fluorescence

Collagen cross-links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age-matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age-related, stable cross-link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride-reducible labile cross-links, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p less than 0.05 and r = 0.684, p less than 0.05, respectively). The results clearly indicate that during the course of ALS, the cross-linking pathway of skin collagen runs counter to its normal aging, resulting in a "rejuvenation" phenomenon of skin collagen. Thus, cross-linking of skin collagen is affected in ALS.

Topics: Aged; Aging; Amyotrophic Lateral Sclerosis; Arm; Borohydrides; Collagen; Desmosine; Dipeptides; Female; Histidine; Humans; Male; Middle Aged; Muscular Diseases; Nervous System Diseases; Oxidation-Reduction; Skin